Assessment of agoraphobia and panic disorder

1. 1. Phobia and panic are defined by the measures used.

2. 2. Rating scales, diaries, global measures, physiological measures, behavioural assessment.

3. 3. Three fear systems: physiological, cognitive and behavioral

4. 4. Concordance and discordance.

5. 5. Synchrony and desynchrony

6. 6. The Behavioural Approach Test at the Calgary General Hospital.

New concepts in benzodiazepine therapy: Rebound anxiety and new indications for the more potent benzodiazepines

1. 1. Abrupt withdrawal of benzodiazepine treatment in generalized anxiety patients was found to induce a rebound anxiety state in addition to minor physical symptoms.

2. 2. Controlled clinical trials suggest that the newer high potency benzodiazepines (alprazolam, clonazepam and bromazepam) have novel psychiatric indications and greater anxiolytic effect than the classical benzodiazepines.

3. 3. Alprazolam, a triazolobenzodiazepine, was superior to placebo in the treatment of panic disorder, for which medium or low potency benzodiazepines are generally inefficacious.

4. 4. Clonazepam, an anticonvulsant which increases 5HT synthesis, was more efficacious than lithium in reducing manic symptoms.

5. 5. Bromazepam, a new potent benzodiazepine, was superior to diazepam in the treatment of generalized anxiety disorder.

Fever and leukocytosis: Physical manifestations of bipolar affective disorder?

1. 1. Fever and leukocytosis are occasionally observed in patients with psychiatric disorders. A thorough medical evaluation does not always reveal the origin of these abnormalities.

2. 2. We report the case histories of three patients with bipolar affective disorder and an abnormal DST who had fever and leukocytosis during the acute phase of their illness. No organic etiology could be found.

3. 3. All three patients responded to ECT with resolution of the depression, the fever, and the leukocytosis, and normalization of the DST.

4. 4. We propose that fever and leukocytosis may be rare physical manifestations of bipolar affective disorder, particularly in patients with abnormal DST.

CGP 11.952: An experimental benzodiazepine derivative. Effects on cognitive functioning in patients with epilepsy

1. 1. In two open studies using patients with intractable epilepsy, the effects of CGP 11.952, a triazolyl benzophenone, on cognitive functioning were assessed by means of a computerized neuropsychological battery.

2. 2. In the first study CGP 11.952 turned out to have a positive effect on information processing speed, perceptual sensitivity and precisaness of responses.

3. 3. Negative effects were found on reaction time.

4. 4. In the second study this latter effect was less clear.

5. 5. A striking result was the less negative effect on memory consolidation under influence of CGP 11.952 in comparison with other benzodiazepines.

Can ECT-induced cognitive effects be altered pharmacologically?

Khan Arifulla, Mary Helen Mirolo, Hugh A. Mirolo and Sheree Miller: Can ECT-Induced Cognitive Effects be Altered Pharmacologically? Prog. Neuro-Psychopharmacol. & Biol. Psychiat. 1993, 17(6): 861–873.

1. 1. A systematic review of the literature revealed twelve clinical trials that evaluated nine different drugs, and used three different conceptual models to prevent, restore or treat ECT-induced cognitive deficits.

2. 2. This review indicated inconclusive results regarding clinical utility of any of the drugs.

3. 3. Major factors discussed include the complexities involved in the evaluation of ECT-induced cognitive deficits, and the techniques of evaluating changes in cognitive functions.

4. 4. Our conclusion is that future research should emphasize understanding the neural mechanisms related to ECT-induced cognitive deficits. We suggest several areas for future exploration.

Differential diagnosis of anxiety disorders

1. 1. The literature comparing panic disorder with natural fear, hypoglycemia, hyperthyroidism, pheochromocytoma, the hyperventilation syndrome, the mitral valve prolapse syndrome and partial complex seizures is briefly reviewed.

2. 2. Some features of each of these syndromes may clinically resemble panic disorder.

3. 3. It is concluded that: a) patients with panic disorder should be medically evaluated. b) the diagnosis of panic disorder should be based on a broad system, rather than on symptoms alone, c) diagnostic systems should include a category for “organic anxiety syndromes”.

Fluoxetine in borderline personality disorder

1. 1. Twelve patients with borderline personality disorder and not suffering a major depression were treated with fluoxetine, a selective serotonin reuptake inhibitor, in an open label trial. All of the patients improved, and 75% were rated as much or very much improved.

2. 2. Treatment was generally very well tolerated, but careful dosage titration was important in some patients, especially to manage agitation.

3. 3. Improvement has been maintained with continued treatment throughout the follow-up period which ranged up to six months.

4. 4. Incidental findings suggest fluoxetine may also be of use in treating substance abuse, attention deficit hyperactivity disorder, late luteal phase dysphoria disorder, dysthymic and cyclothymic disorders, and seasonal pattern depression.

5. 5. These preliminary results support the hypothesis that borderline personality disorder may be related to a central scrotonergic deficit.

Relationship of cognitive ability to the developmental course of antisocial behavior in substance-dependent patients

1. The present study examined cognitive differences among three groups of abstinent substance-dependent patients and a control group of non-drug users. The patient groups were defined according to their DSM III-R substance dependence diagnosis(es): heroin, cocaine, or dual alcohol and cocaine dependence.

2. In the initial analysis, which compared the four subject groups on scores from the Shipley Institute of Living Scale, no significant differences were found. However, the groups did vary on the number of Antisocial Personality Disorder (ASPD) behaviors.

3. Another set of analyses was conducted to examine the relationship between ASPD and SILS scores. Analyses of the effects of ASPD (+/−) across all of the patients revealed lower SILS scores in the ASPD-positive group. Additional analyses examined the developmental course of the ASPD effect by contrasting 1) patient groups characterized by childhood Conduct Disorder (CD) combined with adult ASPD vs. 2) childhood CD which did not continue into adulthood as ASPD vs. 3) adults who did not report childhood CD but who met other ASPD behavioral criteria as adults, vs. 4) subjects who had neither childhood CD nor adult ASPD.

4. In this analysis, it was found that patients who met diagnostic criteria for childhood Conduct Disorder, but whose antisocial behaviors resolved after age 15, had equivalent SILS scores to those patients with no childhood CD or adult ASPD. A decrement in SILS scores was only found in those patients whose antisocial behaviors persisted into adulthood.

5. ASPD adults who did not report childhood CD behaviors had normal SILS scores compared to Controls.

Reduced P3 amplitudes are associated with both a family history of alcoholism and antisocial personality disorder

1. 1. Previous research has demonstrated that the amplitude of the P3 component of the event-related electroencephalographic potential (ERP) is influenced by the presence/absence of a family history of alcoholism (FHA). The present study extended this line of research by examining the P3 effects of both FHA and antisocial personality disorder (ASP) in a 2 × 2 factorial design.

2. 2. The task required subjects to judge the orientation of an infrequently-occurring outline drawing, representing an aerial view of a human head.

3. 3. Analyses of P3 amplitudes elicited by this drawing revealed reductions attributable to the effects of both FHA and ASP, but not their interaction. These effects were most apparent at frontal electrode sites. Analyses of P3 latency revealed no consistent pattern of findings. However, the interval between P3 and manual reaction time was shorter in the ASP+ group relative to the ASP- group.

The association of tardive dyskinesia and pseudoparkinsonism

1. 1. A survey of 315 chronic inpatients for the presence of extrapyramidal side effects indicates that 58.7% of the patients had no evidence of extrapyramidal side effects, 28.6% had tardive dyskinesia (TD) alone, 8.9% had pseudoparkinsonism and 3.8% had a combination of both.

2. 2. Women seemed to exhibit more side effects.

3. 3. Aging was another factor associated with a higher risk for the appearance of extrapyramidal side effects.

4. 4. Affective disorder patients carried more risk than patients with schizophrenia.

5. 5. The low prevalence of the combined TD and pseudoparkinsonism may be related to several factors. The possible explanations are explored and discussed. These patients present a therapeutic dilemna.

Activation of brain function by S-135, a benzodiazepine receptor inverse agonist

1. 1. S-135, 2-(5-methylthien-3-y1)-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one, binds to benzodiazepine receptors with a high affinity and shows pharmacological actions opposite to those of conventional benzodiazepine drugs.

2. 2. S-135 induced no convulsion in mice by itself, but selectively potentiated the effect of subconvulsive dose of pentylenetetrazole.

3. 3. S-135 potentiated rat crossed extensor reflex and Ro 15-1788 completely antagonized this potentiation.

4. 4. S-135 antagonized pentobarbital-induced anesthesia, tetrabenazine-induced ptosis and reserpine-induced hypoactivity and shortened immobilization time in the despair test in mice, indicating that this compound possesses antidepressive properties.

5. 5. S-135 antagonized amnesia in mice and rats in passive avoidance tasks.

6. 6. Glucose utilization in brain areas relating to memory and arousal functions was enhanced following S-135 treatment.

7. 7. These results indicate that S-135 can be a useful drug for activating depressed brain function.

Buspirone: An anxioselective alternative for the management of anxiety disorders

1. 1. Buspirone HCl (Buspar ) is a novel anxiolytic agent unrelated to the benzodiazepines or other psychotherapeutic agents.

2. 2. Animal studies support an anxioselective profile, relief of anxiety without sedation, muscle relaxation or anticonvulsant activity.

3. 3. Double-blind clinical studies show buspirone to be effective in the treatment of anxiety and anxiety in the presence of depression.

4. 4. The effects of buspirone on psychomotor function, physical dependence and abuse potential tests are similar to those seen with placebo treatments.

5. 5. Mechanism of action studies indicate activity in a variety of neuronal systems.

Diagnosis and pharmacotherapy of conduct disorder

Lavin Michael R. and Arthur Rifkin: Diagnosis and Pharmacotherapy of Conduct Disorders. Prog. Neuro- Psychopharmacol. & Biol. Psychiat. 1993, 17(6): 875–885.

1. 1. There are few double-blind, placebo-controlled studies of the drug treatment of conduct disorders in children and adolescents.

2. 2. The diagnosis of conduct disorders involves a persistent pattern of behavior in which the basic rights of others and standards of society are violated.

3. 3. There is frequent comorbidity associated with conduct disorders including attention-deficit hyperactivity disorder, oppositional defiant disorder, mood disorders and substance abuse.

4. 4. Childhood Conduct disorder is associated with a significant risk for adult psychopathology.

5. 5. A variety of treatment approaches may be employed to combat conduct disorders.

6. 6. The use of neuroleptics, lithium carbonate, stimulants and other agents is reviewed.

A double-blind comparison of fluvoxamine, desipramine and placebo in outpatients with depression

Deborah Roth, Jeffrey Mattes, K. Harnett Sheehan and David V. Sheehan: A Double-Blind Comparison of Fluvoxamine, Desipramine and Placebo in Outpatients with Depression. Prog. Neuro-Psychopharmacol. & Biol. Psychiat. 1990, : 929–939.

1. 1. The efficacy of fluvoxamine is compared to that of desipramine in a multicenter double blind placebo controlled six-week flexible dose trial of 90 outpatients with major depressive disorder.

2. 2. Although overall drug effects were relatively weak, there were trends suggesting separation of both active drugs from placebo at week six. Both drugs were well tolerated.

3. 3. Studies of major depression ought to be designed to last 8–10 weeks in order to demonstrate placebo active drug differences and the stability of such a difference should it occur in the first six weeks.

Glycosaminoglycan polysulfate (ateroid) in old-age dementias: effects upon depressive symptomatology in geriatric patients

1. 1. Glycosaminoglycan polysulfate is a mixture of sulfo-muco-polysaccharides with hypolipidemic activity. A number of clinical studies have indicated that it is effective in improving psychopathology in patients with cardiac and/or cerebral disease associated with arteriosclerosis.

2. 2. A multicenter clinical trial was performed to compare the effects of two different dosages of glycosaminoglycan polysulfate upon depressive symptomatology in patients with multi-infarct dementia and primary degenerative dementia.

3. 3. A total of 39 patients were treated in an 18-week clinical trial which followed a singleblind parallel design.

4. 4. Results indicated that patients with both diagnoses improved significantly in depressive symptomatology over the course of treatment, with particular improvement noted in cognitive disturbance. Drug dosage was not a significant determinant of treatment response for either diagnostic group.

Biphasic actions of pentobarbital on synaptic transmission

1. 1. The effects of pentobarbital were studied on synaptic transmission in the rat hippocampal slice preparation.

2. 2. Low concentrations of pentobarbital (0.04–0.1 mM) produced an increase in the Schaffer collateral to CA 1 evoked EPSP and population field potential amplitudes.

3. 3. Higher concentrations of pentobarbital (0.2–1.0 mM) produced depression of field potential amplitudes.

4. 4. Pentobarbital altered synaptic transmission by affecting both pre- and post-synaptic functions.

5. 5. Analysis of input/output curves suggest the presynaptic site is most sensitive.

Determination of plasma haloperidol concentrations by radioreceptor assay in schizophrenia: Clinical utility

1. 1. Haloperidol concentrations were determined by radioreceptor assay (RRA) and prolactin concentrations were measured in 20 patients diagnosed as schizophrenia (DSM-III).

2. 2. The patients were treated with a fixed dose of haloperidol for 21 days.

3. 3. Our results suggest the existence of a curvilinear relationship, in the form of an inverted U, between stable haloperidol levels and clinical improvement assessed by total BPRS score.

4. 4. We also found a curvilinear relationship between the improvement observed in positive symptoms and state steady levels.

5. 5. No relationship was seen between improvement in negative symptoms and state steady levels.

6. 6. An interval of optimal haloperidol concentration was found: 8.1 ng/ml to 19.6 ng/ml.

7. 7. No relation was found between the dose of haloperidol administered and plasmatic concentration, nor between haloperidol and prolactin levels.

8. 8. Our findings suggest that haloperidol concentrations determined by RRA have clinical utility as predictors of response in schizophrenia.

Effects of light on human melatonin production and the human circadian system

1. 1. Bright artificial light appears to have similar effects in humans as in other species.

2. 2. Bright light may therefore be used as a clinical research tool and as a therapeutic modality for treating certain biological rhythm disorders.

3. 3. Melatonin production appears to be a particularly useful “biological marker” for the human endogenous circadian pacemaker and the effects of light.

An experimental antidepressant increases rem sleep

1. 1. An experimental antidepressant was studied through sleep laboratory recordings, psychoendocrinological tests and clinical measurements in terms of its efficacy, side effects and effects on sleep.

2. 2. The design included a four-week drug administration period, proceeded and followed by a one week placebo period.

3. 3. In the presence of antidepressant efficacy, the drug did not disturb sleep induction and maintainance.

4. 4. The only effect on sleep stages was an increase of REM sleep during the short-term drug administration period which is contrary to the REM supressant effect of most antidepressants.

5. 5. This finding suggests that REM supression and antidepressant efficacy are not necessarily related.

6. 6. Further, given that the only known action of the drug is its inhibitory effect on GABA-ergic transmission, one can speculate that GABA mechanisms may be involved in REM sleep modulation.

Folic acid and psychopathology

1. 1. The incidence of folic acid deficiency is high in patients with various psychiatric disorders including depression, dementia and schizophrenia.

2. 2. In epileptics on anticonvulsants, folate deficiency often occurs because anticonvulsants inhibit folate absorption. In these patients folate deficiency is often associated with psychiatric symptoms.

3. 3. In medical patients psychiatric symptoms occur more frequently, and in psychiatric patients symptoms are more severe, in those with folate deficiency than in those with normal levels.

4. 4. Many open studies have demonstrated therapeutic effects of folate administration on psychiatric symptoms in folate deficient patients.

5. 5. Several placebo-controlled studies have not demonstrated therapeutic effects, possibly because the doses they used (15–20 mg/day) are known to be toxic and to cause mental symptoms.

6. 6. Two placebo-controlled studies have demonstrated beneficial effects of Folic acid administration, one in patients with a syndrome of psychiatric and neuropsychological changes associated with folate deficiency and the other in patients on long-term lithium therapy. In the latter study the dose was only 0.2 mg/day.

7. 7. Folic acid deficiency is known to lower brain S-adenosylmethionine and 5-hydroxy-tryptamine. S-Adenosylmethionine, which has antidepressant properties, raises brain 5-hydroxytryptamine. Thus, depression associated with folate deficiency is probably related to low brain 5HT.

8. 8. S-Adenosylmethionine is involved in many methylation reactions, including methylation of membrane phospholipids, which influences membrane properties. This may explain the wide variety of symptoms associated with folate deficiency.

9. 9. Because the costs and risks associated with low doses of folic acid (up to 0.5 mg/day) are small, folic acid should be given as an adjunct in the treatment of patients with unipolar or bipolar affective disorders and anorexia, epileptics on anticonvulsants, geriatric patients with mental symptoms and patients with gastrointestinal disorders who exhibit psychiatric symptoms.

10. 10. Although the majority of the patients listed above will probably not be helped by folic acid therapy, a significant minority are likely to have folate-responsive symptoms.